EarlyTect BCD, a Streamlined PENK Methylation Test in Urine DNA, Effectively Detects Bladder Cancer in Patients with Hematuria.

The current noninvasive diagnostic approaches for detecting bladder cancer (BC) often exhibit limited clinical performance, especially for the initial diagnosis. This study aims to evaluate the validity of a streamlined urine-based PENK methylation test called EarlyTect BCD in detecting BC in patients with hematuria scheduled for cystoscopy in Korean and American populations. The test seamlessly integrates two steps, linear target enrichment and quantitative methylation-specific PCR within a single closed tube.

Mitochondrial PGAM5-Drp1 signaling regulates the metabolic reprogramming of macrophages and regulates the induction of inflammatory responses.

Macrophages play a critical role in the regulation of inflammation and tissue homeostasis. In addition to their vital functions for cell survival and physiology, mitochondria play a crucial role in innate immunity as a platform for the induction of inflammatory responses by regulating cell signaling and dynamics. Dynamin-related protein 1 (Drp1) plays a role in the induction of inflammatory responses and the subsequent development of various diseases.

Evaluation of Sensitive Urine DNA-Based PENK Methylation Test for Detecting Bladder Cancer in Patients with Hematuria.

Hematuria is a prevalent symptom associated with bladder cancer (BC). However, the invasiveness and cost of cystoscopy, the current gold standard for BC diagnosis in patients with hematuria, necessitate the development of a sensitive and accurate noninvasive test. This study introduces and validates a highly sensitive urine-based DNA methylation test.

Identification and validation of methylated PENK gene for early detection of bladder cancer using urine DNA.

Background: Early detection of bladder cancer (BCa) offers patients a favorable outcome and avoids the need for cystectomy. Development of an accurate and sensitive noninvasive BCa diagnostic test is imperative. DNA methylation is an early epigenetic event in the development of BCa.

High Prevalence of Chronic Viral Hepatitis and Liver Fibrosis Among Mongols in Southern California.

Background: Mongolia is a highly endemic region for chronic hepatitis B (HBV), hepatitis delta (HDV), and hepatitis C (HCV) infections. Aim of this study was to comprehensively characterize chronic viral hepatitis among Mongols living in Southern California.

Methods: Three screening events were conducted between August and November 2018, with 528 adult Mongols tested for HBV and HCV.

The protein tyrosine kinase SYK regulates the alternative p38 activation in liver during acute liver inflammation.

Two distinct p38 signaling pathways, classical and alternative, have been identified to regulate inflammatory responses in host defense and disease development. The role of alternative p38 activation in liver inflammation is elusive, while classical p38 signaling in hepatocytes plays a role in regulating the induction of cell death in autoimmune-mediated acute liver injury. In this study, we found that a mutation of alternative p38 in mice augmented the severity of acute liver inflammation.

Hepatic IFN-Induced Protein with Tetratricopeptide Repeats Regulation of HCV Infection.

Interferons (IFNs) suppress viral infection through the induction of >400 interferon-stimulated genes (ISGs). Among ISGs, IFN-induced protein with tetratricopeptide repeats (IFITs) is one of the most potent and well-characterized ISGs. IFIT family consists of 4 cluster genes.

Regulation of Hepatitis C Virus Infection by Cellular Retinoic Acid Binding Proteins through the Modulation of Lipid Droplet Abundance.

Retinoid (vitamin A) is an essential diet constituent that governs a broad range of biological processes. Its biologically active metabolite, all- retinoic acid (ATRA), exhibits a potent antiviral property by enhancing both innate and adaptive antiviral immunity against a variety of viral pathogens, such as, but not limited to, HIV, respiratory syncytial virus (RSV), herpes simplex virus (HSV), and measles. Even though the hepatocyte is highly enriched with retinoid and its metabolite ATRA, it supports the establishment of efficient hepatitis C virus (HCV) replication.

IL-32γ attenuates airway fibrosis by modulating the integrin-FAK signaling pathway in fibroblasts.

Background: Fibrosis in severe asthma often leads to irreversible organ dysfunction. However, the mechanism that regulates fibrosis remains poorly understood. Interleukin (IL)-32 plays a role in several chronic inflammatory diseases, including severe asthma.

Dual modulation of human hepatic zonation via canonical and non-canonical Wnt pathways.

The hepatic lobule is divided into three zones along the portal-central vein axis. Hepatocytes within each zone exhibit a distinctive gene expression profile that coordinates their metabolic compartmentalization. The zone-dependent heterogeneity of hepatocytes has been hypothesized to result from the differential degree of exposure to oxygen, nutrition and gut-derived toxins.

Detection of Occult Hepatitis C Virus Infection in Patients Who Achieved a Sustained Virologic Response to Direct-Acting Antiviral Agents for Recurrent Infection After Liver Transplantation.

Occult infection with hepatitis C virus (HCV) is defined as the presence of the HCV genome in either liver tissue or peripheral blood monocytes, despite constant negative results from tests for HCV RNA in serum. We investigated whether patients who maintained a sustained virologic response 12 weeks after therapy (SVR12) with direct-acting antiviral (DAA) agents for recurrent HCV infection after liver transplantation had occult HCV infections. We performed a prospective study of 134 patients with recurrent HCV infection after liver transplantation who were treated with DAAs, with or without ribavirin, from 2014 through 2016 (129 patients achieved an SVR12).

Organ system view of the hepatic innate immunity in HCV infection.

An orchestration of innate and adaptive immunity determines the infection outcome and whether the host achieves clearance or allows the pathogen to establish persistent infection. The robust activation of the innate immune response plays the most critical role in both limiting viral replication and halting the spread of the pathogen immediately after infection. The magnitude of innate immune activation is coupled with the efficient mounting of the adaptive immunity.

TNF-α enhance Th2 and Th17 immune responses regulating by IL23 during sensitization in asthma model.

Background: TNF-α has been postulated to be a critical mediator contributing to airway inflammation. The purpose of this study was to evaluate the role of TNF-α in the induction of Th17 and Th2 cells related to asthma pathogenesis.

Objective: To evaluate detailed mechanisms for the modulation of IL-23 by TNF-α in sensitization period.

Retinoid regulation of antiviral innate immunity in hepatocytes.

Unlabelled: Persistent infection of hepatitis C virus (HCV) is one of the leading causes of end-stage liver disease (ESLD), such as decompensated cirrhosis and liver cancer. Of particular note, nearly half of HCV-infected people in the United States are reported to be heavy drinkers. This particular group of patients is known to rapidly progress to the ESLD.

Regulation of NKT cell-mediated immune responses to tumours and liver inflammation by mitochondrial PGAM5-Drp1 signalling.

The receptor-interacting protein kinase 3 (RIPK3) plays crucial roles in programmed necrosis and innate inflammatory responses. However, a little is known about the involvement of RIPK3 in NKT cell-mediated immune responses. Here, we demonstrate that RIPK3 plays an essential role in NKT cell function via activation of the mitochondrial phosphatase phosphoglycerate mutase 5 (PGAM5).

Tissue-Specific Regulation of p38α-Mediated Inflammation in Con A-Induced Acute Liver Damage.

Because p38α plays a critical role in inflammation, it has been an attractive target for the development of anti-inflammation therapeutics. However, p38α inhibitors showed side effects, including severe liver toxicity, that often prevailed over the benefits in clinical studies, and the mechanism of toxicity is not clear. In this study, we demonstrate that p38α regulates the inflammatory responses in acute liver inflammation in a tissue-specific manner, and liver toxicity by p38α inhibitors may be a result of the inhibition of protective activity of p38α in the liver.

Eosinophils Modulate CD4(+) T Cell Responses via High Mobility Group Box-1 in the Pathogenesis of Asthma.

Eosinophils have been reported to modulate T cell responses. Previously, we reported that high-mobility group box 1 protein (HMGB1) played a key role in the pathogenesis of asthma. This study was conducted to test our hypothesis that eosinophils could modulate T cell responses via HMGB1 in the pathogenesis of asthma characterized by eosinophilic airway inflammation.

Clusterin expression level correlates with increased oxidative stress in asthmatics.

Background: Oxidative stress is thought to play a role in the pathogenesis of asthma. Clusterin is a sensitive cellular biosensor of oxidative stress and has antioxidant properties. The function and expression of clusterin in patients with asthma have not been fully investigated.

Interleukin-32γ suppresses allergic airway inflammation in mouse models of asthma.

Asthma is a chronic airway inflammatory disease typically associated with T helper cell type 2 (Th2) cytokines. IL-32, first reported as an inducer of tumor necrosis factor (TNF)-α, is an inflammatory cytokine involved in various autoinflammatory diseases, viral infection, and cancer-related inflammation. However, the role of IL-32γ in asthma has not been clearly elucidated.

The TNF family member 4-1BBL sustains inflammation by interacting with TLR signaling components during late-phase activation.

Activation of Toll-like receptor (TLR)-dependent signaling leads to the expression of genes encoding proinflammatory factors, such as tumor necrosis factor-α (TNF-α), and this proinflammatory gene expression is sustained for the duration of the inflammatory response. TLR4-mediated inflammation, which occurs in two phases, depends on the TNF family member 4-1BB ligand (4-1BBL) to sustain TNF-α production during late-phase signaling. We showed that Toll-interleukin-1 receptor (TIR) domain-containing adaptor protein (TIRAP) and the kinase IRAK2 interacted with 4-1BBL to mediate late-phase TLR4 signaling.

IL-13 and STAT6 signaling involve in low dose lipopolysaccharide induced murine model of asthma.

Background: We reported that level of lipopolysaccharide (LPS) exposure determined the type of airway inflammation in a murine model of asthma.

Objective: The purpose of this study is to evaluated the role of IL-13 in low dose LPS induced murine model of asthma using IL-13 and signal transducer and activator of transcription 6 (STAT6) deficient mice.

Methods: Mice were sensitized with an intranasal application of LPS-depleted ovalbumin (OA) and different doses of LPS (0.

Metformin reduces airway inflammation and remodeling via activation of AMP-activated protein kinase.

Recent reports have suggested that metformin has anti-inflammatory and anti-tissue remodeling properties. We investigated the potential effect of metformin on airway inflammation and remodeling in asthma. The effect of metformin treatment on airway inflammation and pivotal characteristics of airway remodeling were examined in a murine model of chronic asthma generated by repetitive challenges with ovalbumin and fungal-associated allergenic protease.

Grape seed proanthocyanidin extract attenuates allergic inflammation in murine models of asthma.

Background: Antioxidants have been suggested to alleviate the pathophysiological features of asthma, and grape seed proanthocyanidin extract (GSPE) has been reported to have powerful antioxidant activity.

Purpose: This study was performed to determine whether GSPE has a therapeutic effect on allergic airway inflammation in both acute and chronic murine model of asthma.

Methods: Acute asthma model was generated by intraperitoneal sensitization of ovalbumin (OVA) with alum followed by aerosolized OVA challenges, whereas chronic asthma model was induced by repeated intranasal challenges of OVA with fungal protease twice a week for 8 weeks.

Dexamethasone-induced FKBP51 expression in peripheral blood mononuclear cells could play a role in predicting the response of asthmatics to treatment with corticosteroids.

Background: Corticosteroids (CSs) are the preferred anti-inflammatory therapy for the treatment of asthma, but the responses of asthmatics to CSs are known to vary. It has thus become important to discover reliable markers in predicting responses to CSs.

Methods: We performed time-series microarrays using a murine model of asthma after a single dose of dexamethasone, based on the assumption that the gene showing a greater change in response to CSs can also be a potential marker for that finding.

TH2 and TH1 lung inflammation induced by airway allergen sensitization with low and high doses of double-stranded RNA.

Background: Although respiratory viral infections in early childhood can enhance the development of airway allergen sensitization, the exact mechanisms of the effects of viral infections on the adaptive immune response to inhaled allergens are controversial.

Objective: We sought to evaluate the effects of double-stranded RNA (dsRNA) on airway sensitization to inhaled allergens.

Methods: Novel mouse models were created through simultaneous airway sensitization to an allergen and low or high doses of dsRNA.